We are carrying out trials in adults with drug resistant hairy cell leukemia and in children with acute lymphoblastic leukemia. In a phase 1 trial in adults in which Robert Kreitman is the principal investigator, we have found that an intravenous dose of 50 ug//Kg is safe and has produced more than a 50% complete remissions in Hiary Cell Leukemia. Based on this data the FDA has given permission for a pivotal trial to open and 3 patients have now been treated. In ALL the phase 1 trial is still ongoing and has been modified so children can receive 10 doses each cycle. In some patients complete remissions have been observed on this regimen. We have completed a phase 1 trial with SS1P in which Raffit Hassan is the principal investigator. In this trial SS1P was given with permetrexed/cis platinum, the standard mesothelin therapy; the response rate in this trial is higher that the published responses observed with chemotherapy alone. A randomized phase 2 trial to confirm this finding is being planned. Because SS1P is immunogenic and neutralizing antibodies usually form after 1 treatment cycle, we have carried out a trial in which SS1P is combined with 2 immunosuppressive drugs, pentostatin and cytoxan in patients who have failed standard therapy for mesothelioma. We have been able to give additional cycles to these patients and in addition have observed several major anti-tumor responses. This trial is now being expanded.